Design, synthesis, and biological evaluation of 1-benzylamino-2-hydroxyalkyl derivatives as new potential disease-modifying multifunctional anti-Alzheimer's agents
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60162694%3AG44__%2F18%3A43889537" target="_blank" >RIV/60162694:G44__/18:43889537 - isvavai.cz</a>
Nalezeny alternativní kódy
RIV/00179906:_____/18:10375709
Výsledek na webu
<a href="https://pubs.acs.org/doi/10.1021/acschemneuro.7b00461" target="_blank" >https://pubs.acs.org/doi/10.1021/acschemneuro.7b00461</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acschemneuro.7b00461" target="_blank" >10.1021/acschemneuro.7b00461</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Design, synthesis, and biological evaluation of 1-benzylamino-2-hydroxyalkyl derivatives as new potential disease-modifying multifunctional anti-Alzheimer's agents
Popis výsledku v původním jazyce
The multitarget approach is a promising paradigm in drug discovery, potentially leading to new treatment options for complex disorders, such as Alzheimer's disease. Herein, we present the discovery of a unique series of 1-benzylamino-2-hydroxyalkyl derivatives combining inhibitory activity against butyrylcholinesterase, beta-secretase, amyloid, and tau protein aggregation, all related to mechanisms which underpin Alzheimer's disease. Notably, diphenylpropylamine derivative 10 showed balanced activity against both disease-modifying targets, inhibition of beta-secretase (IC50 hBACE-1 = 41.60 mu M), inhibition of amyloid beta aggregation (IC50, beta = 3.09 mu M), inhibition of tau aggregation (55% at 10 mu M); as well as against symptomatic targets, butyrylcholinesterase inhibition (IC50 (hBuchE) = 7.22 mu M). It might represent an encouraging starting point for development of multifunctional disease-modifying anti-Alzheimer's agents.
Název v anglickém jazyce
Design, synthesis, and biological evaluation of 1-benzylamino-2-hydroxyalkyl derivatives as new potential disease-modifying multifunctional anti-Alzheimer's agents
Popis výsledku anglicky
The multitarget approach is a promising paradigm in drug discovery, potentially leading to new treatment options for complex disorders, such as Alzheimer's disease. Herein, we present the discovery of a unique series of 1-benzylamino-2-hydroxyalkyl derivatives combining inhibitory activity against butyrylcholinesterase, beta-secretase, amyloid, and tau protein aggregation, all related to mechanisms which underpin Alzheimer's disease. Notably, diphenylpropylamine derivative 10 showed balanced activity against both disease-modifying targets, inhibition of beta-secretase (IC50 hBACE-1 = 41.60 mu M), inhibition of amyloid beta aggregation (IC50, beta = 3.09 mu M), inhibition of tau aggregation (55% at 10 mu M); as well as against symptomatic targets, butyrylcholinesterase inhibition (IC50 (hBuchE) = 7.22 mu M). It might represent an encouraging starting point for development of multifunctional disease-modifying anti-Alzheimer's agents.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
30104 - Pharmacology and pharmacy
Návaznosti výsledku
Projekt
—
Návaznosti
N - Vyzkumna aktivita podporovana z neverejnych zdroju
Ostatní
Rok uplatnění
2018
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
ACS Chemical Neuroscience
ISSN
1948-7193
e-ISSN
—
Svazek periodika
9
Číslo periodika v rámci svazku
5
Stát vydavatele periodika
US - Spojené státy americké
Počet stran výsledku
21
Strana od-do
1074-1094
Kód UT WoS článku
000432752400021
EID výsledku v databázi Scopus
2-s2.0-85047190249